Recently, the CDC announced that COPD had escalated to the 3rd leading cause of death in this country. John Walsh (President, COPD Foundation) remarked that It's unacceptable that COPD has gone from the fourth leading cause to the third twelve years sooner than what was originally projected. Although there have been significant advances in care, the COPD epidemic persists, leading to more than 120,000 deaths/yr. in the US alone. This emphasizes the serious knowledge gap that continues to exist in the detection and evaluation of general lung function. The overall goal of this research project is to develop and validate both qualitative and quantitative regional evaluation of lung function with non-invasive MR based biomarkers using perfluorinated gases as ventilation contrast agents. The significance of this project is if we could detect regional variations in lung volume and function prior to global ventilation changes (e.g. spirometric measures) or clinical symptoms (e.g. exacerbations), we could perform therapeutic interventions while the affected area of the lung is still 'recoverable'. The unmet clinical need is that currently Standard of Care for diagnosis and evaluation of lung disease relies nearly exclusively on global PFT information (essentially a 'single volume' element, the entire communicating airway system) and that improvements in diagnosis and treatment depend on better and regional strategies for lung imaging that are deployable with moderate technical impact and cost. We have already shown that breathable fluorinated gases (PFx's) provide an entirely new and inexpensive MR-based approach to 3D ventilation imaging in humans. Our preliminary work has shown that these agents are well tolerated; enable imaging ventilation with a quality similar to that of natural abundance hyperpolarized 129Xe MRI. The central hypothesis and current observation is that PFx gases used as contrast agents provide functional images of the lung airways including important regional ventilation information such as ventilation defect severity and gas trapping. We will test the central hypothesis and accomplish the overall objective by addressing the following aims 1) determine quantitative measures of lung ventilation including gas trapping, 2) define ventilation defect severity and 3) compare gas trapping from PFx imaging to HRCT in a well characterized subject cohort. The technical innovations include the use of single-breath non-equilibrium imaging and multi-breath equilibrium imaging techniques to evaluate not only 'static' ventilation defects but also ventilation defect severity. The outcomes of the work include a novel approach for evaluation of regional lung function in humans that does not use ionizing radiation and is more easily disseminated than hyperpolarized technology. PUBLIC HEALTH RELEVANCE: The economic burden of COPD in the US in 2010 was estimated at 29.5 billion dollars in direct costs with an additional 20.5 billion in other costs suh as productivity loss. It is easily the largest uncontrolled disease epidemic in the US. This program aims to validate perfluorinated gas imaging markers of regional distribution of the disease to improve therapy development and patient management.